Pharmacophore model prediction, 3D-QSAR and molecular docking studies on vinyl sulfones targeting Nrf2-mediated gene transcription intended for anti-Parkinson drug design

TL;DRAbstract

Despite intense research efforts towards clinical and molecular causes of Parkinson disease (PD), the etiology of disease still remains unclear. However, recent studies have provided ample evidences that the oxidative stress is the key player that contributes a lot to dopaminergic (DAergic) neurodegeneration in brain. It is due to the discrepancy of antioxidant defence system of which nuclear factor erythroid 2-related factor 2 (Nrf2) signalling is of central contour. In the current study, potent heme oxygenase-1 agonists (Nrf2 signalling regulator), vinyl sulfones, were selected and an optimal pharmacophore model was brought forth which was examined using a decoy set by atom-based 3D-QSAR. The best four-feature model consists of two hydrogen bond acceptors and two aromatic rings, which has the highest correlation coefficient, R(2) = .71 and [Formula: see text] = .73 in QSAR. These ligands were further studied for molecular docking with Nrf2-keap protein to gain insight into the major

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